Focal Irreversible Electroporation

Whilst most prostate cancers occupy large areas of the prostate, there are some that occupy less than half and often less than a quarter of the prostate gland. These more focal prostate cancers probably constitute about 20% of all prostate cancers. With high quality 3T multiparametric MRI combined with template 3D transperineal biopsies and sometimes combined with PSMA PET scanning, it is now much more possible to identify this select group of patients. The advantage of focal treatments of the prostate with energy sources such as the NanoKnife allow eradication of the cancer with minimal side effects.

Whole-gland therapies such as surgery, radiotherapy and brachytherapy have a long and established track record in the treatment of multifocal and high grade prostate cancer. However, their use in more focal cancers may be regarded as overtreatment based on recent data from a large randomised trial ( PROTECT trial ). Furthermore, radical prostatectomy, radiotherapy and brachytherapy have a significant side effect profile including urinary incontinence, impotence and rectal damage which are largely avoided by focal NanoKnife therapy.

After a full workup to ensure that our patients are suitable for the program they then undergo a day surgery procedure which takes between 40 and 60 minutes. Depending on the extent of the cancer this may simply ablate the lesion, a quarter of the prostate or a half of the prostate. No prostate cancer cells are resistant to this treatment. Large areas can be treated with minimal side effects.

After the treatment patients stay in the day surgery unit for two to four hours and they are discharged home with a Foley catheter in place. Postoperatively pain is minimal and patients are discharged with tablets for mild pain, moderate pain, bladder spasms and relaxation of the prostate and antibiotics as required.

On day 2 a limited multiparametric MRI is performed. The Foley catheter is left in for two to five days depending on the extent of the treatment.

• Focal gleason large-volume Gleason 6 prostate cancer, Gleason 3+4=7 focal prostate cancer and Gleason 4+3=7 focal prostate cancer and select low-volume Gleason 4+4 prostate cancer.
• PSA < 15
• MRI identifiable tumour which correlates perfectly with targeted biopsies.
• Template biopsies confirmed no significant prostate cancer outside of this region or outside of that side of the prostate.
• Patient refuses standard therapies such as surgery, radiotherapy and brachytherapy.
• Patient over 55 and preferably over 60.
• Patient fit for general anaesthesia.
• Patient accepts the need for ongoing monitoring.

Focal Ire Versus Robot-Assisted Nerve-Sparing Surgery

FOCAL IRE	NERVE-SPARING ROBOT-ASSISTED SURGERY
Minimally invasive	Keyhole surgery
Day surgery procedure.	One to two days in hospital
Two to five day Foley catheter.	Six day Foley catheter
Minimal recovery	Three to six week recovery
Mild discomfort.	Mild to moderate pain.
<1% Major Complications	< 1% major complications.
0% incontinence	1-2% ongoing incontinence.
< 10% impotence rate	10-30% impotence (recovery period required).
Suitable for unifocal tumours	Suitable for multifocal tumours.
<20% recurrence rate.	PSA recurrence between 10 and 30% depending on extent of tumour.
Can be repeated.	Cannot be repeated
Needs active ongoing surveillance

• Focal IRE treatment for the treatment of localised prostate cancer is safe.
  
• IRE is 97% effective in the eradication of the index lesion of the prostate.
  
• There is a < 15% recurrence rate in the rest of the prostate at five years of followup.
  
• IRE has low toxicity and lower common side effects compared to established treatments.
  
• IRE is suitable for recurrences after radiation therapy.
  
• Major complications have not occurred in our series of 200 patients with up to five year followup.
  
• MRI is useful in the followup of patients however it misses between 10 and 20% of recurrences which can only be picked up by transperineal biopsy.
  
• IRE ideally is used selectively in focal intermediate grade prostate cancer to avoid over treatment by more conventional treatments
  
• Multifocal intermediate and high grade prostate cancer generally are much more serious conditions than focal intermediate grade prostate cancer and until IRE can be shown to have equal cancer cure rates compared to surgery and radiotherapy in this higher risk group, more conventional methods such as surgery and radiation therapy should be used.

Valerio, M, Stricker PD, H. U. Ahmed, L. Dickinson, L. Ponsky, Shnier R, C. Allen, and M. Emberton. 2014. Initial assessment of safety and clinical feasibility of irreversible electroporation in the focal treatment of prostate cancer. Prostate Cancer Prostatic Dis, 17: 343 https://doi.org/10.1038/pcan.2014.33

Ting F, M. Tran, M. Böhm, Siriwardana A, van Leeuwen PJ, Haynes AM, Delprado W, Shnier R, and Stricker PD. 2015. Focal irreversible electroporation for prostate cancer: functional outcomes and short-term oncological control. Prostate Cancer And Prostatic Diseases, 19: 46. https://doi.org/10.1038/pcan.2015.47

Ting F, van Leeuwen PJ, and Stricker PD. 2016. Step-by-Step Technique for Irreversible Electroporation of Focal Prostate Cancer: An Instructional Video Guide. J Vasc Interv Radiol, 27: 568. https://doi.org/10.1016/j.jvir.2016.01.003

Scheltema M.J, van den Bos W, Siriwardana AR, Kalsbeek AMF, Thompson JE, Ting F, Bohm M, Haynes AM, Shnier R, Delprado W, and Stricker PD. 2017. Feasibility and safety of focal irreversible electroporation as salvage treatment for localized radio-recurrent prostate cancer. BJU Int, 120 Suppl 3: 51-58. https://doi.org/10.1111/bju.13991

Scheltema MJ, Chang JI, Bohm M, van den Bos W, A. Blazevski, Gielchinsky I, Kalsbeek AMF, van Leeuwen PJ, Nguyen TV T. M. de Reijke, Siriwardana AR, Thompson JE, J. J. de la Rosette, and Stricker PD. 2018. Pair-matched patient-reported quality of life and early oncological control following focal irreversible electroporation versus robot-assisted radical prostatectomy. World J Urol. https://doi.org/10.1007/s00345-018-2281-z

Van den Bos W, Scheltema MJ, Siriwardana AR, Kalsbeek AMF, Thompson JE, Ting F, Bohm M, Haynes AM, Shnier R, Delprado W, and Stricker PD. 2018. Focal irreversible electroporation as primary treatment for localized prostate cancer. BJU Int, 121: 716-24. https://doi.org/10.1111/bju.13983

Scheltema MJ, Chang JI, van den Bos W, Gielchinsky I, Nguyen TV T. M. Reijke, Siriwardana AR, Bohm M, J. J. de la Rosette, and Stricker PD. 2018. Impact on genitourinary function and quality of life following focal irreversible electroporation of different prostate segments. Diagn Interv Radiol, 24: 268-75. https://doi.org/10.5152/dir.2018.17374

Scheltema M.J, T. J. O’Brien, van den Bos W, D. M. de Bruin, R. V. Davalos, C. W. M. van den Geld, M. P. Laguna, R. E. Neal, 2nd, I. M. Varkarakis, A. Skolarikos, Stricker PD, T. M. de Reijke, C. B. Arena and J. de la Rosette (2019). umerical simulation modeling of the irreversible electroporation treatment zone for focal therapy of prostate cancer, correlation with whole-mount pathology and T2-weighted MRI sequences. Ther Adv Urol 11: 1756287219852305. https://doi.org/10.1177/1756287219852305

Blazevski, A, Scheltema MJ, A. Amin, Thompson JE, N. Lawrentschuk and Stricker PD (2019). rreversible electroporation (IRE): a narrative review of the development of IRE from the laboratory to a prostate cancer treatment. BJU Int. https://doi.org/10.1111/bju.14951

Blazevski A, Scheltema MJ, Yuen B Masand N, Nguyen TV W.Delprado, Shnier R, A. Haynes, Cusick T, Thompson J, Stricker P. Oncological and Quality-of-life Outcomes Following Focal Irreversible Electroporation as Primary Treatment for Localised Prostate Cancer: A Biopsy-monitored Prospective Cohort. Eur Urol. Oncol(2019). https://doi.org/10.1016/j.euo.2019.04.008

Blazevski, A, Scheltema MJ, A. Amin, Thompson JE, N. Lawrentschuk and Stricker PD (2020). Irreversible electroporation (IRE): a narrative review of the development of IRE from the laboratory to a prostate cancer treatment. BJU Int 125(3): 369-378. https://doi.org/10.1111/bju.14951

Blazevski A, Amin A, Scheltema MJ, Balakrishnan A, Haynes AM, Barreto D, Cusick T, Thompson J, Stricker PD. Focal ablation of apical prostate cancer lesions with irreversible electroporation (IRE). World J Urol. 2021 Apr;39(4):1107-1114. https://doi.org/10.1007/s00345-020-03275-z  Epub 2020 Jun 2.

Cussenot O, Stricker PD. Irreversible electroporation for patients with localised prostate cancer: Expert opinion on this versatile therapeutic approach. EMJ Urol. 2021 Aug:9[1]:56-62. https://www.emjreviews.com/urology/article/irreversible-electroporation-for-patients-with-localised-prostate-cancer-expert-opinion-on-this-versatile-therapeutic-approach-j180121

Blazevski A, Gondoputro W, Scheltema MJ, Amin A, Geboers B, Barreto D, Haynes AM, Shnier R, Delprado W, Agrawal S, Thompson JE, Stricker PD. Salvage robot-assisted radical prostatectomy following focal ablation with irreversible electroporation: feasibility, oncological and functional outcomes. BMC Urol. 2022 Mar 2;22(1):28. https://doi.org/10.1186/s12894-022-00978-w.

Geboers B, Gondoputro W, Thompson JE, Reesink DJ, van Riel LAMJG, Zhang D, Blazevski A, Doan P, Agrawal S, Matthews J, Haynes AM, Liu Z, Delprado W, Shnier R, de Reijke TM, Lawrentschuk N, Stijns PEF, Yaxley JW, Scheltema MJ, Stricker PD. Diagnostic Accuracy of Multiparametric Magnetic Resonance Imaging to Detect Residual Prostate Cancer Following Irreversible Electroporation-A Multicenter Validation Study. Eur Urol Focus. 2022 May 13:S2405-4569(22)00106-7. https://doi.org/10.1016/j.euf.2022.04.010. Epub ahead of print.

van Riel LAMJG, Geboers B, Kabaktepe E, Blazevski A, Reesink DJ, Stijns P, Stricker PD, Casanova J, Dominguez-Escrig JL, de Reijke TM, Scheltema MJ, Oddens JR. Outcomes of salvage radical prostatectomy after initial irreversible electroporation treatment for recurrent prostate cancer. BJU Int. 2022 Apr 27. https://doi.org/10.1111/bju.15759. Epub ahead of print.

Ong S, Chen K, Grummet J, Yaxley J, Scheltema MJ, Stricker P, Tay KJ, Lawrentschuk N. Guidelines of guidelines: focal therapy for prostate cancer, is it time for consensus? BJU Int. 2022 Sep 9. https://doi.org/10.1111/bju.15883. Epub ahead of print.

Scheltema M.J, Geboers, B, Blazevski, A, Doan, P, Katelaris, A, Agrawal, S, Barreto, D, Shnier, R, Delprado, W, Thompson, J. E, & Stricker, P. D. (2022). Median 5-year outcomes of primary focal irreversible electroporation for localised prostate cancer. BJU international, 10.1111/bju.15946. Advance online publication. https://doi.org/10.1111/bju.15946

Blazevski, A, Geboers, B, Scheltema M.J, Gondoputro, W, Doan, P, Katelaris, A, Agrawal, S, Baretto, D, Matthews, J, Haynes, A. M, Delprado, W, Shnier, R, Van den Bos W, Thompson, J. E, Lawrentschuk, N, & Stricker, P. D. (2022). Salvage irreversible electroporation for radio-recurrent prostate cancer – the prospective FIRE trial. BJU international, 10.1111/bju.15947. Advance online publication. https://doi.org/10.1111/bju.15947

Geboers, B, Scheltema M.J, Blazevski, A, Katelaris, A, Doan, P, Ali, I, Agrawal, S, Barreto, D, Matthews, J, Haynes, A. M, Delprado, W, Shnier, R, Thompson, J. E, & Stricker, P. D. (2023). Median 4-year outcomes of salvage irreversible electroporation for localized radio-recurrent prostate cancer. BJU international, 10.1111/bju.15948. Advance online publication. https://doi.org/10.1111/bju.15948

Emberton M, Reijke T;, Stricker P, Miñana, Bianco F, Dominguez Escrig J, Lantz A, Sanchez-Salas R. Revisiting Delphi to create a basis for the future of focal therapy for prostate cancer. Urology Journal URL-D-23-00730

Lantz A, Nordlund P, Falagario U, Jäderling F, Özbek O, Clements M, Discacciati A, Grönberg H, Eklund M, Stricker P, Emberton M, Aly M, Nordström T. Prostate Cancer IRE Study (PRIS): A Randomized Controlled Trial Comparing Focal Therapy to Radical Treatment in Localized Prostate Cancer. Eur Urol Open Sci. 2023 Apr 8;51:89-94. https://doi.org/10.1016/j.euros.2023.03.003 . PMID: 37091033; PMCID: PMC10114162.

Deivasigamani S, Kotamarti S, Rastinehad AR, et al. Primary Whole-gland Ablation for the Treatment of Clinically Localized Prostate Cancer: A Focal Therapy Society Best Practice Statement. Eur Urol. 2023;84(6):547-560. https://doi.org/10.1016/j.eururo.2023.06.013. Epub ahead of print. PMID: 37419773.

Scheltema MJ, Katelaris A, Stricker PD. Salvage irreversible electroporation for radio-recurrent prostate cancer. Nat Rev Urol. 2023 Mar 1. https://doi.org/10.1038/s41585-023-00750-1 . Epub ahead of print. PMID: 36859611.

Rodríguez-Sánchez L, Emberton M, de Reijke T, Stricker P, Miñana B, Bianco F, Escrig JLD, Lantz A, Sanchez-Salas R. Revisiting Delphi to Create a Basis for the Future of Focal Therapy for Prostate Cancer. World J Mens Health. 2023 Oct 16. DOI: 10.5534/wjmh.230160. Epub ahead of print. PMID: 37853538.

Zhang K, Stricker P, Löhr M, Stehling M, Suberville M, Cussenot O, Lunelli L, Ng CF, Teoh J, Laguna P, de la Rosette J. A multi-center international study to evaluate the safety, functional and oncological outcomes of irreversible electroporation for the ablation of prostate cancer.  Prostate cancer and prostatic diseases. 2024 Jan 9. https://doi.org/10.1038/s41391-023-00783-y”. Epub ahead of print. PMID: 38195916.

Geboers B, Meijer D, Counter W, et al. Prostate-specific membrane antigen positron emission tomography in addition to multiparametric magnetic resonance imaging and biopsies to select prostate cancer patients for focal therapy. BJU Int. 2024;133 Suppl 4:14-22. https://doi:10.1111/bju.16207

Williams ISC, Katelaris A, Geboers B, Doan P, Delprado W, Scheltema MJ, Stricker P. Transrectal Ultrasound as Real-Time Confirmation of Adequate Needle Positioning During Irreversible Electroporation in Focal Therapy of Prostate Cancer. Videourology 37, pp. 1 – 2 https://doi.org/10.1089/vid.2023.0046

Geboers B, Scheltema MJ, Jung J, Stricker PD. Irreversible Electroporation of Intermediate risk prostate cancer mitigates immune suppression and induces systemic antitumor T cell activation Presented at USANZ Annual Scientific Meeting 2024

1. Stricker PD. Nanoknife focal therapy. Invited speaker. 3rd Friends of Israel Urological Symposium 5-7th July 2016. Tel-Aviv, Israel.
2. Tran M, Jackson B, Boehm M, Haynes A-M, Stricker P, Irreversible Electroporation for Focal Prostate Cancer: Safety, Short-term Functional and Oncological Outcomes. Poster Presentation. 68th Urological Society of Australia and New Zealand Annual Scientific Meeting 11th – 19th April 2015, Adelaide, South Australia
3. Van den Bos W, Stricker PD et al. Focal Therapy Using IRE in prostate cancer. Synergy Miami, November 2016. Miami Beach, Florida USA.
4. Siriwardana A, van den Bos W, Kalsbeek A, Thompson J, Ting F, Boehm M, Haynes A, Shnier R, Delprado W and Stricker PD. Focal Irreversible Electroporation (IRE) as a primary and salvage treatment for localised prostate cancer. USANZ 2017 Annual Scientific Meeting 24-27th February 2017, Canberra, Australia
5. Scheltema, MJ, van den Bos W, Siriwardana AR, Kalsbeek AMF. Thompson JE, Ting F, Bohm M, Haynes AM, Shnier R, Delprado W, Stricker PD. Focal Irreversible Electroporation as primary and salvage treatment for prostate cancer. 5th Global Congress on Prostate Cancer. 28 – 30 June 2017, Lisbon Portugal
6. Scheltema MJ, Chang JI, van den Bos, Bohm M, Delprado W, Gielchinsky I, de Reijke TM, de la Rosette J, Sirawardana AR, Shnier R, Stricker PD. Diagnostic Accuracy of Mulitparametric Resonance Imaging Following Prostate Cancer Focal Therapy with Irreversible Electroporation. 93rd Annual Meeting Western Section of the American Urological Association, 6 -10 August 2017, Vancouver British Columbia Canada
7. Scheltema MJ, Chang JI, van den Bos, Gielchinsky I, de Reijke TM, Sirawardana AR, Bohm M, de la Rosette J, Stricker PD. Genito-Urinary Function and Quality of Life after Focal Irreversible Electroporation of Different Prostate Segments. 93rd Annual Meeting Western Section of the American Urological Association, 6 -10 August 2017, Vancouver British Columbia Canada
8. Scheltema MJ, Chang JI, Bohm B, van den Bos W, Gielchinsky I, Kalsbeek AF, van Leeuwen PJ, de Reijke TM, Siriwardana AR, de la Rosette JJ. Stricker PD. Pair-matched Patient-reported Quality of Life following Focal Irreversible Electroporation versus Robot-assisted Radical Prostatectomy. 37th Congress of the Societe Internationale d’Urologie. 19-22 October 2017, Lisbon Portugal.
9. Stricker PD Focal Nanoknife Therapy Invited speaker Tolmar National Symposium
10. Blazevski, A (On behalf of P Stricker) - Ideal framework for the introduction of Nanoknife - 38th Congress of the Société Internationale d’Urologie, 2018, Seoul, Korea
11. Blazevski A, Yuen B, Scheltema MJ, Masand N, Haynes AM, Nguyen Q, Stricker P. Oncological Outcomes of Focal Irreversible Electroporation as Primary Treatment for Clinically Significant Localised Prostate Cancer. 38th Congress of the Société Internationale d’Urologie. 2018, Seoul, Korea
12. Blazevski A, Yuen B, Scheltema MJ, Chang J, Masand N, Haynes AM, Nguyen Q, Stricker P. Is it time for prostate cancer’s lumpectomy? Focal irreversible electroporation (IRE) for localised clinically significant prostate cancer. 26th ASMR NSW ASM 2018
13. Blazevski A, Pidsley R, Qu W, Norbie D, Luu L, Chang J, Yuen B, Scheltema MJ, Masand N, Haynes AM, Nguyen Q, Stirzaker C, Song J, Stricker P, Clark S. When Focal Therapy Fails for Localised Prostate Cancer – Can Epigenetics Predict Which Patients Fail and Improve Patient Selection? ANZUP ASM 8 – 10 July 2018. Sydney, Australia.
14. Blazevski A, Yuen B, Scheltema MJ, Chang J, Masand N, Haynes AM, Nguyen Q, Stricker P. Focal irreversible electroporation as salvage treatment for localised radio-recurrent prostate cancer – Initial results and initiation of the FIRE trial. ANZUP ASM 8 – 10 July 2018. Sydney, Australia.
15. Stricker P, Blazevski A, Scheltema MJ, Thompson J, Haynes AM, Nyguen Q, Chang, J, Yuen B. Oncological outcomes of irreversible electroporation (Nanoknife) for localised clinically significant prostate cancer at single Australia centre. 6th Edition Global Congress on Prostate Cancer (PROSCA 2018). 28 – 30 June 2018. Frankfurt, Germany
16. Blazevski A, Yuen B, Scheltema MJ, Chang J, Masand N, Haynes AM, Nguyen Q, Stricker P. Is it time for prostate cancer’s lumpectomy? – Focal irreversible electroporation (IRE) for localised clinically significant prostate cancer. ASMR NSW Annual Scientific Meeting, June 2018. Sydney, Australia.
17. Blazevski A, Yuen B, Scheltema MJ, Chang K, Masand N, Haynes AM, Nguyen Q, Stricker P. 5 years of Irreversible Electroporation (Nanoknife) for Localised Prostate Cancer. Asia-Pacific Prostate Conference 2018. Brisbane, Australia.
18. Blazevski A, Stricker P. Where is the prostate cancer recurrence after radiation therapy? Implications for biopsy and focal salvage therapy. USANZ NSW Section Meeting. 1 – 3 November 2018. Cypress Lakes, Hunter Valley, NSW, Australia.
19. Stricker, P - Key note speaker for salvage prostate cancer treatment - Hadassah Medical Center, Jerusalem, 2018
20. Stricker, P - Introduction of NanoKnife to Amsterdam - National Cancer Institute – 2018
21. Blazevski A, Scheltema MJ, Yuen B, Masand N, Haynes AM, Cusick T, Stricker P. Focal Irreversible Electroporation for Radiorecurrent Prostate Cancer – Update on Current Results and Establishment of the FIRE trial. TROG Annual Scientific Meeting 2019. Melbourne, Australia
22. Blazevski A, Scheltema MJ, Yuen B, Masand N, Haynes AM, Cusick T, Stricker P. Update on 12-Month Biopsy Proven Oncological and Functional Outcomes of Primary Irreversible Electroporation for Localised Prostate Cancer. USANZ Annual Scientific Meeting 2019. Brisbane, Queensland
23. Blazevski A, Scheltema MJ, Yuen B, Masand N, Haynes AM, Cusick T, Stricker P. Salvage Irreversible Electroporation for Locally Recurrent Prostate Cancer after Radiotherapy – Oncological and Functional Outcomes. USANZ Annual Scientific Meeting 2019. Brisbane, Queensland
24. Amin A, Blazevski A, Scheltema MJ, Thompson J, Stricker P. Salvage Radical Prostatectomy After Focal Irreversible Electroporation for Prostate Cancer: A Case Series Reporting Oncological Outcomes. Société International d’Urologie 2019 – Athens.
25. Blazevski A, Scheltema MJ, Yuen B, Masand N, Haynes AM, Cusick T, Shnier R, Stricker P. Diagnostic accuracy of multiparametric magnetic resonance imaging to detect residual prostate cancer following focal therapy with irreversible electroporation. AUA 2019 – Annual Scientific Meeting – Chicago.
26. Blazevski A, Cusick T, Haynes AM, Stricker P. Evolution of Irreversible Electroporation into a prostate cancer treatment – From the laboratory to Urologists. AUA 2019 – Annual Scientific Meeting – Chicago.
27. Blazevski A, Scheltema MJ, Yuen B, Masand N, Haynes AM, Cusick T, Stricker P. Salvage irreversible electroporation for locally recurrent prostate cancer after radiotherapy – Oncologic and functional outcomes. EAU 2019 – Annual Scientific Meeting – Barcelona.
28. Blazevski A, Scheltema MJ, Yuen B, Masand N, Haynes AM, Cusick T, Stricker P. Update on 12-month biopsy-proven oncological and functional outcomes of primary irreversible electroporation for localised prostate cancer. EAU 2019 – Annual Scientific Meeting – Barcelona.
29. Blazevski A, Scheltema MJ, Yuen B, Masand N, Haynes AM, Cusick T, Shnier R, Stricker P. Diagnostic accuracy of multiparametric magnetic resonance imaging to detect residual prostate cancer following focal therapy with irreversible electroporation. EAU 2019 – Annual Scientific Meeting – Barcelona
30. Geboers B, Scheltema MJ, Jung J ... Stricker PD. Irreversible Electroporation of Intermediate risk prostate cancer mitigates immune suppression and induces systemic antitumor T cell activation Presented at USANZ Annual Scientific Meeting 2024